April 17, 2023 Sporos BioDiscovery, Inc. (a wholly owned affiliate of Sporos Bioventures, "Sporos" or the "Company"), a precision oncology company developing a diversified pipeline of small molecule therapeutic candidates, reported preclinical data for its lead candidate, SPR1-0117, a next-generation TEAD inhibitor at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, FL.

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SPR1-0117 targets cancers driven by mutations in the Hippo pathway, a key regulator of cell proliferation and oncogenesis not yet extensively targeted in precision oncology. The YAP1/TAZ co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4), execute the pro-cancerous effects of the Hippo pathway through transcription of pro-proliferative and anti-apoptotic genes. Hippo pathway activation has also emerged as a key mechanism of resistance to inhibitors of the MAPK pathway, making TEAD inhibitors a prime candidate for combination therapy with therapeutics targeting the MAPK pathway.

Sporos BioDiscovery’s bioinformatic analyses identified that selective inhibition of both TEAD1 and TEAD4 drives improved biological impact as compared to TEAD1 inhibitors alone, while inhibition of TEAD2 and TEAD3 were observed as undesirable due to the potential for paradoxical adverse stimulation of cell proliferation and kidney toxicity, respectively.

"We are excited to share this new data demonstrating the deep and broad biological activity of SPR1-0117 both in vitro and in vivo, not only in benchmark models of cancers driven by Hippo-pathway mutations but in a number of cell lines beyond that of mesothelioma and NF2 mutations, including in cell lines showing only a nuclear YAP/TAZ hyperactivity. We believe this broad activity is driven by SPR1-0117’s isoform selectivity profile which inhibits both TEAD1 / TEAD4. We believe this profile may unlock the potential of SPR1-0117 as a monotherapy in a wide array of tumors with Hippo driver mutations compared to inhibitors binding primarily TEAD1," said Stephen Rubino, Ph.D., Chief Executive Officer of Sporos Bioventures.

Dr. Rubino continued "We also see greater depth of biological response in benchmark models, with close to 80% frank regression in large, established tumors, a feat unaccomplished by other TEAD inhibitors to date. Overall, we believe SPR1-0117’s TEAD1 / TEAD4 isoform selectivity profile has been optimized as a potential best-in-class TEAD inhibitor for both monotherapy and in combination with MAPK and RTK inhibitors. We are on track to initiate IND-enabling studies for our TEAD inhibitor program this quarter and look forward to advancing our lead candidate into the clinic in 2024."

Data reported in the poster presentation from AACR (Free AACR Whitepaper) demonstrated SPR1-0117 has showed strong monotherapy activity across multiple in vitro models, including several non-mesothelioma cell lines. In addition, SPR1-0117 shows low nM potency and strong single-agent activity against TEAD-dependent benchmark in vivo models, including H226 NF2-null mesothelioma, as well as in vivo efficacy beyond mesothelioma in SCC25, an oral squamous cell carcinoma. SPR1-0117 has also demonstrated a promising ADME and safety profile in preclinical models and was shown to be well tolerated, including no significant findings of kidney toxicity, in a seven-day repeat dosing study in rats at greater than 10-times the drug exposure required for efficacy in mice.

(Press release, Sporos BioDiscovery, APR 17, 2023, View Source [SID1234662115])

On April 17, 2023 AbClon, a South Korean biotech firm, reported the company presented non-clinical and phase 1 interim results of its AT101 novel CAR-T therapy at the annual 2023 AACR (Free AACR Whitepaper) conference (Press release, AbClon, APR 17, 2023, View Source [SID1234638627]). AT101 targets the CD19 protein for treatment of blood cancer.

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AT101 demonstrated superior anti-cancer efficacy compared to FMC63-based CAR-T therapies in non-clinical data. AT101 utilizes the h1218 antibody, developed through AbClon’s Novel Epitope Screening Technology (NEST), and binds in a unique manner to CD19. AT101 demonstrated efficacy even in CD19 mutant cancer cell models that did not respond to FMC63-based CAR-T therapies. Overall, AT101 has the potential to provide new treatment opportunities for patients including those who do not respond to currently available CAR-T therapies.

An open-label, non-randomized, multicenter phase 1 study was conducted at three different dose levels in patients with relapsed / refractory B-NHL. The results of the first two dose levels in Phase 1, low and medium, have been determined. For medium dose, although the dosage administered to patients is lower than that of currently available CAR-T therapies, all three patients achieved complete response (CR) four weeks after administration. Even at 5-fold lower dosage to medium dose, CR was observed in 3 out of 6 patients and partial response (PR) was observed in 2 patients. Cytokine release syndrome (CRS) and neurotoxicity (ICANS), which appear as side effects of CAR-T therapy, were also observed at low levels of 11.1% and 22.2%. In particular, the rate of 3 or higher grade on side effects was 11.1%, showing encouraging signs with regard to safety. Clinical trial of high dosage level is currently in progress.

AT101 was administered to patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Effective responses to AT101 potentiate the application of AT101 for different types of hematologic malignancies.

Research teams led by Professor Marco Ruella of Perelman School of Medicine at University of Pennsylvania, Professor Junho Chung of Seoul National University College of Medicine, and Professor Dok hyun Yoon of Asan Medical Center are participating in this study.

AbClon owns independent intellectual property rights for the technologies applied to AT101 and is currently building channels for global expansion with local partners. AT101 patent registration has been completed in U.S., Canada, Japan, and South Korea. Further registrations are underway in Europe and China.

Jong-Seo Lee, CEO of AbClon, said, "AT101 showed promising results in r/r B-NHL patients, including multiple CRs in the dose escalation stage and excellent safety. We are hopeful for ongoing trials of AT101 to provide more affordable and effective treatment opportunities to patients fighting blood cancer."

For more information on the ongoing trial, refer to the ClinicalTrials.gov Identifier: NCT05338931

Details of the presentation are as follows:

Presentation Title: An open label, dose escalation, phase 1 study of AT101, a novel CD19-directed CAR-T cell therapy targeting a membrane-proximal epitope of CD19, in patients with relapsed or refractory B cell non-Hodgkin lymphoma
Session Title: Phase I Clinical Trials in Progress

About AT101
AT101 is a CAR-T therapy that targets CD19 protein for blood cancer.

AbClon has initiated a Phase 1/2 clinical study of AT101 in adults with relapsed or refractory B-cell non-Hodgkin lymphoma (NCT05338931)

Phase 1/2 study is being conducted in Asan Medical Center and Ulsan University Hospital under the support of the Korea Drug Development Fund (KDDF) in Korea.

On April 17, 2023 Myricx Pharma, an oncology drug discovery company focused on developing precision medicines based on its N-myristoyltransferase (NMT) platform has unveiled its antibody drug conjugate (ADC) programme, reported in vivo data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Annual Meeting, AACR (Free AACR Whitepaper) 2023, April 14-19, Florida (Press release, MyricxBio, APR 17, 2023, View Source [SID1234635232]).

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NMT inhibitors (NMTi) have previously been shown to inhibit viability and growth of haematological cancers. Myricx’s novel highly potent NMTi are selectively cytotoxic in multiple cancer cell lines as well as exhibiting tumour regression in in vivo models of both haematological and solid cancers. Myricx has also developed a transcriptional signature which predicts cancer cell sensitivity to NMTi with high confidence.

Myricx’s advanced chemistry offers the potential for the development of NMTi as a novel payload on a wide range of existing linker and antibody ADC technologies. A unique feature of NMTi-ADCs is that they contain two targeting mechanisms: a monoclonal antibody (mAb) that targets the payload to antigen positive cancer cells; and selectivity for specific cancers with high intrinsic sensitivity to NMTi. Myricx has data elucidating the mechanism of this sensitivity.

Myricx’s most advanced ADC, MYX2449, is a selective and ultrapotent NMTi conjugated via a cleavable linker to trastuzumab (HER2+ mAb). Positive in vitro and in vivo data presented at AACR (Free AACR Whitepaper)2 demonstrate MYX2449 cytotoxic potency in selective cancer cell lines, anti-tumour efficacy in both high and low HER2 expressing cancers, with tolerability >10 times its efficacious dose in in vivo models.

As a proof of concept (PoC) for its NMTi-ADC approach, Myricx tested MYX2449 trastuzumab-NMTi ADC in in vivo models of gastric cancer (GC) and breast cancer (BC), as many of these cancers express HER2 and also express the NMTi sensitivity signature. MYX2449 delivered differentiated activity and improved efficacy compared to the gold standard ADC trastuzumab-deruxtecan in a GC model with excellent tumour shrinkage at 5mpk in the xenograft and excellent cyno tolerability at the highest dose, 20mpk. Similar efficacy was obtained in a BC xenograft model.

Encouraged by these positive PoC results, Myricx is now exploring a range of ADCs in further hard-to-treat solid cancers that express both the NMTi sensitivity signature and ADC-compatible antigens.

Myricx CEO Dr Robin Carr who presented the ADC-NMTi poster at AACR (Free AACR Whitepaper) said "NMT inhibitors represent a novel class of ADC payloads that can be exploited as targeted therapies in cancer. Based on our positive PoC data we believe that ADC-NMTi offer huge potential for selective cancer cell killing via its unique mechanism of action."

Myricx is a start-up from two of London’s leading biomedical research organizations, Imperial College London and the Francis Crick Institute. Myricx scientists and founding collaborators were the first to identify that inhibition of NMT is highly effective in the treatment of MYC-driven cancer models acting through the unfolded protein response (UPR). UPR stress is a known vulnerability of cancer and Myricx is now using its discoveries to build a proprietary pipeline of targeted cancer therapies. The company is developing NMTi as small molecule drugs as well as novel selective cytotoxic payloads for ADCs.

In addition to the poster on its lead ADC programme, scientists from Myricx’s collaborators presented two posters on Myricx’s small molecule programmes and NMT biology, including in vivo reprogramming of tumour-associated macrophages to an anticancer phenotype by modulating NMT activity1 and how deregulation of MYC-family proteins sensitizes cancers to NMT inhibition, resulting in the identification of NMTi sensitivity and mechanism.3

Professor Ed Tate, Myricx co-founder and lead author of the posters presented by the Imperial College London/Francis Crick Institute teams said "NMT is a hot emerging drug target in cancer and Myricx has developed high-quality proprietary chemical inhibitors of NMT that have led to breakthrough discoveries and unlocked an unexpected and unique mechanism of cancer cell killing, specific to cancers with vulnerabilities associated with the unfolded protein response. Furthermore, we have recently shown that NMTi has the potential to drive anti-tumour innate immune responses, including the reprogramming of tumour-associated macrophages in the tumour microenvironment.

"These discoveries alongside the massive potential of NMTi as a selective ADC payload pave the way for novel and highly efficacious treatments for patients."

1. Poster number: 439: From foe to friend: In vivo reprogramming of tumour-associated macrophages to an anti-cancer phenotype by modulating N-myristoyltransferase activity – presented by @Wouter Kallemeijn, Francis Crick Institute/Imperial College London
New Drug Targets 16 April 1:30 PM Section 16 board 3

2. Poster number: 2635: N-Myristoyltransferase (NMT) inhibitors as novel potent payloads for antibody drug conjugates – presented by our CEO @Robin Carr
Antibody Technologies session 17 April, 1:30 PM Section 13 board 3

3. Poster number: 4871: Dysregulation of MYC-family proteins sensitizes cancers to NMT inhibition: identification of NMTi sensitivity and mechanism – presented by @James Zhang, ICR/Imperial College London
Anticancer Approaches Targeting Signal Transduction Pathways 18 April 1:30 PM Section 13 board 14

Copies of these posters will be available on our website after they have been presented – view posters

On April 17, 2023 Etira reported multiple abstracts related to their licensed products showed encouraging preclinical activity in metastatic breast cancer and ovarian cancer (Press release, EtiraRx, APR 17, 2023, View Source [SID1234632165]). The data, presented at The American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, demonstrate strong efficacy in multiple preclinical models both in vitro and in vivo.

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"We are excited by the positive preclinical results for both ERX-208 and ERX-41 recently presented at AACR (Free AACR Whitepaper). Our studies validate our prior finding that targeting LIPA to induce endoplasmic reticulum stress can effectively overcome tumor heterogeneity in ovarian cancer cells," said Russell Hayward, Chief Executive Officer of Etira. "We are especially encouraged by preclinical data that demonstrates ERX-208 is a highly potent agent against ovarian cancer and can be advanced to clinical trials. We are also excited by the preclinical data supporting the use of a chemically distinct analog TX-245 in metastatic breast cancers driven by the mutant estrogen receptor. These findings support our pipeline of agents for additional indications, as we continue to advance ERX-315 to clinical trials."

Presentations included:
1. ERX-208 as a novel therapeutic for treating ovarian cancer by enhancing endoplasmic reticulum stress (poster)
Presenter: Suryavathi Viswanadhapalli
Conclusions: The data demonstrated the utility of ERX-208 in ovarian cancer to overcome tumor heterogeneity by targeting LIPA and enhancing endoplasmic reticulum stress leading to apoptosis. ERX-208 reduced the growth of OCa patient derived organoids in vitro, patient derived explants ex vivo and xenografts including patient derived xenografts in vivo. ERX-208 treatment did not show any signs of toxicity at doses administered.

2. Novel LIPA targeted therapy for treating ovarian cancer (poster)
Presenter:Alexia B. Collier
Conclusions: These studies indicate that ERX-41 effectively binds to and targets LIPA, induces endoplasmic reticulum stress and apoptosis of multiple types of ovarian cancer cells. Detailed molecular characterization of how ERX-41 binding to LIPA induces ER stress in OCa cells is ongoing.

3. Targeting the mutant estrogen receptor in metastatic breast cancer (talk)
Presenter:Karla Parra
Conclusions:TX-245, which was designed to bind to the mutant estrogen receptor, effectively inhibits cell proliferation in cell lines that express WT or mutant ESR1, induce ER degradation, suppress ER-mediated signaling and reduce tumor burden in mouse models. Importantly, TX-245 inhibited the progression of metastatic tumors, indicating its potential utility in patients with metastatic breast cancer expressing the mutant estrogen receptor.

On April 17, 2023 Champions Oncology, Inc. (NASDAQ:CSBR), a leading global technology-enabled research organization that is transforming drug discovery through innovative AI-driven pharmaco-pheno-multiomic (PPMO) integration, reported the launch of its therapeutic discovery and development platform into a wholly owned subsidiary named Corellia AI (Corellia) (Press release, Champions Oncology, APR 17, 2023, View Source [SID1234630517]). Corellia launches out of Champions Oncology with a team of world class scientists advancing a robust pipeline of therapeutic programs and a unique discovery and development platform. The company will continue to leverage Champions’ superior PDX Molecular Atlas and its living bank of PDX models as central tools in its proprietary target and therapeutic discovery platform.

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The comprehensive discovery platform established by Corellia boasts AI-mediated technology that yields an extremely deep and continuously growing pool of novel therapeutic targets, and AI-guided technology for the discovery of novel therapeutic chemistry. Corellia’s objective is to develop innovative first-in-class Antibody Drug Conjugates (ADCs) for patients with high unmet needs, at a pace and efficiency never achieved before.

Ronnie Morris, MD, President and CEO of Champions Oncology, who will also serve as Executive Chairman of Corellia AI said "I’m thrilled about the formation of Corellia. The therapeutic discovery initiative at Champions has been an exciting endeavor that utilizes our deep data. This team has been very effective at identifying interesting novel targets and has rapidly built therapeutic programs around these targets. So, launching this into a wholly-owned subsidiary has been a natural next step, and will allow us to facilitate future growth. I look forward to seeing the continued growth and success of this organization as we enter this next phase."

"The evolution of Champions’ therapeutic discovery and development initiative into an early-stage biotech has been a thrilling experience," said Michael Ritchie, PhD, M.B.A, Chief Commercial Officer at Champions Oncology who will serve as Chief Executive Officer of Corellia AI. "The discovery platform built by the Corellia team is truly unique, and it has enabled the development of an exciting set of early therapeutic programs. We have plans to aggressively move these programs into the clinic and leverage our unparalleled platform to continue building a very deep pipeline of additional therapeutic programs. Our current focus is on the development of transformative and novel next-generation Antibody Drug Conjugates, and the Corellia platform is capable of much more in the future."